PB2204: HIGH SERUM FERRITIN AT INITIAL DIAGNOSIS IS A PREDICTOR OF BONE MARROW FIBROSIS IN PH NEGATIVE CHRONIC MYELOPROLIFERATIVE NEOPLASMS
Authors: Aldo Leone, Raffaella Reina, Martina Romano, Francesco Muriano, Giuseppe Gaeta, Raffaella Iannotta, Giuseppina Donnarumma, Italia Conversano, Serafina Barbato, Rossella Iula, Andrea Cacace, Vincenzo Martinelli, Fabrizio Pane, Novella Pugliese
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Among hematologic malignancies, the Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are considered a model of inflammation-related cancer development. Serum ferritin can be considered a widely used surrogate inflammation marker. Only one report (O.Yokus et al., Am. J. Blood Res.) assessed the association between serum ferritin at diagnosis, splenomegaly and bone marrow fibrosis in overt myelofibrosis (MF). Aims: Here we described the distribution of ferritin levels at baseline among all four MPNs subgroups (ET, PV, pre-MF, MF) and the association of serum ferritin with bone marrow (BM) fibrosis, splenomegaly and both driver and not-driver mutations. Methods: Our cohort included 101 patients who received MPN diagnosis between 2017 and 2022 at Federico II (Napoli – Italy) with the availability of a baseline NGS performed on peripheral blood or bone marrow; only patients with no history of blood transfusions were included. The NGS “myeloid panel” included the 3 driver genes (JAK-2, CALR and MPL) and 23 not-driver genes: ASXL1, CBL, CEPBA, CSF3R, DMNT3A, ETV6, EZH2, HRAS, IDH1/2, cKIT, KRAS, NRAS, PTPN11, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53, U2AF1, WT1, ZRSR2. Splenomegaly was assessed by baseline ultrasound. BM fibrosis was evaluated at histological examination according to Thiele grading. The statistical analysis was performed with SPSS Statistics v. 2.0. Pearson Chi-Square test, T-Test, Kurskal-Wallis test and ANOVA were used to compare differences among subgroups. Results: Our cohort included 63 males and 38 females. The most frequent diagnosis was ET (50%), followed by PV (33%), pre-MF (9%) and MF (8%). Median age was 57 years (range 17-79) in all groups, but MF had a higher median age at diagnosis (70 years, range 56-82). Median serum ferritin (ng/mL) levels at diagnosis were 27,5 in PV (range 4-336), 74,5 in ET (range 5-420), 202 in pre-MF (range 5-545) and 233 in MF (range 43-930). The statistical analysis found that MF had higher ferritin levels compared to PV (p 0.004) and ET (p 0.01) and pre-MF compared to PV (0.005) and ET (p 0.02); there was no difference between MF and pre-MF (p 0.79). Higher ferritin levels were also associated with splenomegaly (median ferritin 140.4 in patients with splenomegaly vs. 76.6 for patients with normal spleen volume, p 0.02) and ASXL1 mutations (170.5 ng/mL for ASXL1 mutated vs. 85.2 ng/mL for ASXL1 unmutated, p 0.011). Incidentally, ASXL1 was more frequent in MF compared to PV (p <.001), ET (p <.001) and pre-MF (p 0.02).Furthermore, a linear correlation was observed between baseline ferritin and bone marrow fibrosis grading (table 1). Summary/Conclusion: In this study we confirmed the association of higher serum ferritin with MF and splenomegaly. We reported for the first time an increased ferritin also in pre-MF compared to PV and ET and the association of ferritin with bone marrow fibrosis grading and ASXL1 mutations. This data could be explained by the low iron stores usage due to MF and pre-MF ineffective erythropoiesis. However, ASXL1 gene is known for modifying the TGF-ß expression: more studies are needed to clarify this association, but we could speculate that TGF-ß is a cytokine reported to be involved both in the bone marrow fibrosis pathogenesis and in regulating the expression of epcidin mRNA, the most important regulator of iron metabolism. Therefore, ASXL1 mutations could have a role in promoting bone marrow fibrosis, explaining the higher frequency of this mutation in MF and the strong association found between serum ferritin and bone marrow fibrosis. Keywords: Ferritin, Myelofibrosis, Myeloproliferative disorder, Polycythemia vera